dc.contributor.author |
Miralles Socías, Antonio
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dc.contributor.author |
Esteban Valdés, Susana Cristina
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dc.contributor.author |
Sastre-Coll, Antonio
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dc.contributor.author |
Moranta Mesquida, David
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dc.contributor.author |
Asensio Landa, Antonio José
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dc.contributor.author |
García-Sevilla Jesús Andrés
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dc.date.accessioned |
2018-09-18T08:59:55Z |
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dc.identifier.uri |
http://hdl.handle.net/11201/147493 |
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dc.description.abstract |
[eng] This study was designed to determine the affinity and binding profile of h-carbolines for imidazoline I2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (h-carboline) and LSL 60101 (I2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [3H]2-BFI revealed that h-carbolines recognize the high- and low-affinity components of the brain imidazoline I2 receptor with the rank order of potency (KiH in nM): noreleagnine (12)>norharman (20)>harmalol (82)>harmaline (177)>harmine (630)>harman (700)HFG-7142 (>100,000). In liver, this rank was different: harmine (51)>harmaline (103)=noreleagnine (103)Hharmalol (1290)>harman (2000)Hnorharman (12,382)HFG-7142 (>100,000). In brain and liver, competition curves for h-carbolines against [3H]Ro41-1049 (MAO-A) and [3H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)-precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that h-carbolines bind with high affinity to imidazoline I2B receptors, and similarly to I2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal. |
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dc.format |
application/pdf |
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dc.relation.isformatof |
Versió postprint del document publicat a: |
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dc.relation.ispartof |
European Journal of Pharmacology, 2005, vol. 518, num. (2-3), p. 234-242 |
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dc.rights |
(c) Elsevier B.V., 2005 |
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dc.subject.classification |
612 - Fisiologia |
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dc.subject.classification |
615 - Farmacologia. Terapèutica. Toxicologia. Radiologia |
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dc.subject.other |
612 - Physiology. Human and comparative physiology |
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dc.subject.other |
615 - Pharmacology. Therapeutics. Toxicology |
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dc.title |
High affinity binding of β-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: Norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain |
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dc.type |
info:eu-repo/semantics/article |
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dc.type |
info:eu-repo/semantics/acceptedVersion |
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dc.date.updated |
2018-09-18T08:59:56Z |
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dc.date.embargoEndDate |
info:eu-repo/date/embargoEnd/2075-01-01 |
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dc.embargo |
2075-01-01 |
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dc.subject.keywords |
receptor de imidazolina |
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dc.subject.keywords |
Adicción a opiáceos |
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dc.subject.keywords |
Monoaminas |
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dc.subject.keywords |
síndrome de abstinència |
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dc.rights.accessRights |
info:eu-repo/semantics/embargoedAccess |
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